Can you explain what goes on in the brain to make people depressed? I've read about serotonin and dopamine, but I'm still not sure why one person gets depressed and another one doesn't.

I’ll try, but it's very complicated, and my brief answer may not be very satisfying. Depression is truly a biopsychosocial illness, and as the term suggests, all three pathways are important — the biological, the psychological, and the social. The initial theories of the biology of depression centered on the monoamine neurotransmitters — norepinephrine, serotonin, and to a lesser extent, dopamine — because these neurotransmitters were known to be involved in the regulation of sleep, energy, appetite, and pleasure and because the first antidepressant medications were found to rapidly increase concentrations of these neurochemicals in the brain.

Much more has been learned about the complexities of brain function in the past 40 or so years, and many other neurochemicals have been implicated in depression. There has also been a shift away from research on particular neurotransmitters in favor of studies investigating changes in the activity and interrelationships among various regions of the brain, which can be viewed as being akin to electrical circuits. This approach has been made possible by the introduction of increasingly more sensitive techniques to visualize the living brain (that is, neuroimaging techniques such as positron-emission tomography, or PET, and functional magnetic resonance imaging, or fMRI).

The changes in the brain that are associated with depression, as observed by the above-mentioned techniques, largely reflect extreme or exaggerated forms of normal adaptive responses to acute stress. Moreover, across species, one common response to prolonged unresolvable stress is a type of exhaustion of central nervous system resources. One type of stress is emotionally mediated, and both sadness and fear are relevant emotions in this form of stress. Fear — the normal emotional response to threat or impending danger — is the counterpart of anxiety and sadness, which are associated with depression, a normal human emotional response to loss.

With respect to depression, relevant losses include those that result from defeat or disappointment in the social or work spheres of our lives, and those that accompany the breaking of an intimate interpersonal bond, such as the grief that follows the death of a loved one, or the “broken heart” that follows a romantic breakup or divorce.

Recent research has confirmed that the “cause and effect” relationship between life stress and risk of depression is greatest early in the course of a depressive illness (that is, during the first or second episode of depression) and tends to diminish with repeated episodes. This suggests that the vulnerability to depression changes over time and that some people will begin to suffer recurrent episodes of depression out of the blue.

It has also long been known that depression and anxiety “run in families” — that they can result from genetic factors as well as such early adversity as emotional, physical, or sexual abuse. There is no single gene, however, that determines depression risk; rather, a number of genes have been associated with an increased risk of depression, including several genes involved in the regulation of serotonin and aspects of stress response.

 One pathway of inherited vulnerability appears to be an increased sensitivity to stress. That said, there may also be inherited resilience factors, which can increase the protective effects of social support and actually reduce a person's risk of depression during stressful times.